STAT3 is an oncoprotein which participates in essential processes of cell survival, growth and proliferation in many types of tumors, as well as immune diseases[3]. Brevilin A is a sesquiterpene lactone isolated from Centipeda minima with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 µM) in cancer cells[3]. In vivo investigation suggested that brevilin A significantly inhibited the growth of CT26 tumor compared to adriamycin and concurrently promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues[4]. Brevilin A increased ROS levels, decreased MMP and induced apoptosis of CT26 cell in a dose-dependent manner. Higher apoptotic rates were achieved in CT26 cells treated with 2 μg/ml brevilin A compared to 2 μg/ml adriamycin, with a statistical significance of both compounds compared to control, indicating that brevilin A exerts a greater capacity in cell apoptosis induction than adriamycin[4]. Brevilin A significantly down-regulated the phosphorylation of PI3K, AKT and mTOR, and promoted the expression of LC3-II, which was a key protein in cell autophagy, in addition to the expression of autophagy-related proteins Beclin1 and Atg5, which indicated that PI3K/AKT/mTOR signaling was involved in CT26 autophagy induced by brevilin A[4]. Tumor weights of mice treated with brevilin A and adriamycin for 14 days were significantly lower compared to the control group (p < .01, p < .05) while the weight of those treated with brevilin A were significantly lower than that of the adriamycin group (p < .01). Body weights in adriamycin group were clearly lower than brevilin A group (p < .01), indicating that brevilin A exhibites lower toxicity compared to adriamycin[4]. The growth inhibition of the tumors by brevilin A reached 74.89% on day 14 after the inoculation, but the inhibition of tumor growth by adriamycin was 53.18%. In contrast with the control, brevilin A significantly promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues[4].
Brevilin A 细胞实验
Cell Line
Concentration
Treated Time
Description
References
RAW264.7 macrophages (TNFα/IFNγ stimulated)
1, 2, 5 μM
1 h
Significantly inhibited TNFα/IFNγ-induced NO production
Front Pharmacol. 2022 Jun 14;13:911157
BMDMs (bone-marrow derived macrophages)
1, 2, 5 μM
1 h
Significantly inhibited LPS/IFNγ-induced NO production
Front Pharmacol. 2022 Jun 14;13:911157
RAW264.7 macrophages
1, 2, 5 μM
1 h
Inhibited NO and PGE2 production, downregulated iNOS and COX2 expression, suppressed mRNA expression of IL-1β, IL-6, and TNFα
Front Pharmacol. 2022 Jun 14;13:911157
A549/T lung cancer cells
5, 10, 15 µM
24 h
Brevilin A significantly inhibited the proliferation and growth of A549/T cells and induced apoptosis.
Front Pharmacol. 2022 Feb 24;13:795613
Madin-Darby canine kidney (MDCK) epithelial cells
8 µM
4-8 h
Inhibited replication of H1N1, H3N2, and H9N2 influenza viruses, reduced viral RNA synthesis, viral mRNA expression, and nuclear export of viral ribonucleoproteins (vRNPs).
Viruses. 2019 Sep 8;11(9):835
A549 cells
0, 20, 30, 40, 50 µM
12 h
To evaluate the ability of BLN-A to induce apoptosis, results showed that BLN-A induced apoptosis in A549 cells in a dose-dependent manner.
J Cancer. 2020 Apr 6;11(13):3725-3735
NCI-H1650 cells
0, 5, 15, 30, 60, 100 µM
12 h
To evaluate the inhibitory effect of BLN-A on cell proliferation, results showed that BLN-A inhibited the proliferation of NCI-H1650 cells in a dose-dependent manner.
J Cancer. 2020 Apr 6;11(13):3725-3735
A549 cells
0, 5, 15, 30, 60, 100 µM
12 h
To evaluate the inhibitory effect of BLN-A on cell proliferation, results showed that BLN-A inhibited the proliferation of A549 cells in a dose-dependent manner.
To evaluate the effect of Brevilin A on the viability of NCM460 cells, results showed that Brevilin A exhibited relatively less cytotoxicity to colon epithelial cells compared to CRC cells.
J Transl Med. 2023 Apr 16;21(1):260
HT-29
16.70 μM (24h), 3.05 μM (48h)
24h and 48h
To evaluate the effect of Brevilin A on the viability of HT-29 cells, results showed that Brevilin A reduced CRC cell viability in a dose-dependent manner.
J Transl Med. 2023 Apr 16;21(1):260
LOVO
8.73 μM (24h), 2.82 μM (48h)
24h and 48h
To evaluate the effect of Brevilin A on the viability of LOVO cells, results showed that Brevilin A reduced CRC cell viability in a dose-dependent manner.
J Transl Med. 2023 Apr 16;21(1):260
CT26
21.53 μM (24h), 9.67 μM (48h)
24h and 48h
To evaluate the effect of Brevilin A on the viability of CT26 cells, results showed that Brevilin A reduced CRC cell viability in a dose-dependent manner.
J Transl Med. 2023 Apr 16;21(1):260
HCT-116
20.98 μM (24h), 8.94 μM (48h)
24h and 48h
To evaluate the effect of Brevilin A on the viability of HCT-116 cells, results showed that Brevilin A reduced CRC cell viability in a dose-dependent manner.
J Transl Med. 2023 Apr 16;21(1):260
Brevilin A 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR and C57BL/6 mice
LPS-induced acute lung injury model
Intraperitoneal injection
20 mg/kg
Administered 2 h before LPS exposure, and again at 6 and 18 h after LPS challenge
Attenuated LPS-induced lung damage, inflammatory infiltration, and production of pro-inflammatory cytokines (MPO, IL-1β, IL-6, TNFα, and PGE2)
Front Pharmacol. 2022 Jun 14;13:911157
BALB/c mice
Influenza A/PR/8/34 (H1N1) virus infection model
Intraperitoneal injection
25 mg/kg
Starting 1 hour post-infection, once every other day for 6 days
Evaluated the protective effect of Brevilin A in influenza virus-infected mice, showing that the 25 mg/kg dose group significantly delayed time-to-death with 50% survival up to 14 days post-infection.
Viruses. 2019 Sep 8;11(9):835
BALB/c mice
CRC liver metastasis model and xenograft model
Intraperitoneal injection
4 mg/kg and 8 mg/kg
Once daily for 2 consecutive weeks
To evaluate the effect of Brevilin A on CRC liver metastasis and tumor growth, results showed that Brevilin A significantly inhibited colorectal liver metastasis and cancer growth.
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